Protein quality control and Disease
Swedish Foundation for Strategic Research
Parkinson's disease & PD-related disorders
Cells are highly compartmentalized into numerous membrane-bound organelles such as the Endoplasmic reticulum and mitochondria. The membranes that define each organelle contain unique sets of embedded proteins that impart distinct functionalities to that organelle A major goal of this proposal is to understand how this compartmentalization is achieved with high fidelity, and how it is regulated to suit constantly changing cellular demands. Mislocalization of proteins is a constant problem faced by the cell. When mislocalization of certain proteins becomes excessive, it can lead to various diseases including neurodegeneration. Thus, the quality control pathways that selectively recognize and degrade these proteins are crucial to maintaining cellular homeostasis and avoiding disease. The studies proposed in this application aims at understanding the protein quality control and degradation. In the first part, I will explore the role of the of the cytosolic quality control machinery in elimination of mislocalized ER secretory and membrane proteins. In the second part I will study mitochondrial quality control and the role of ER-Mitochondria contacts in Parkinsons disease. I will employ a range of techniques, including biochemical dissection of in vitro reconstituted pathways and molecular genetic studies in cultured cells. We anticipate that our mechanistic studies will shed light on both a fundamental cell biological problem and the molecular basis of various diseases.